The purpose of this project is (a) a detailed investigation of the metabolism of vitamin D in humans under normal and pathological conditions and (b) an assessment of the biological effectiveness of the newly characterized vitamin D metabolite, 1,25-dihydroxycholecalciferol and also 25-hydroxycholecalciferol. It is clear from studies in rats and chicks that it is a metabolite of vitamin D and not the parent vitamin, per se, which elicits the physiological responses normally attributable to vitamin D. Although the two major polar metabolites of vitamin D have been characterized, it is not clear how effective these compounds are in humans. Accordingly the present work will be directed toward obtaining a definition of the metabolism of vitamin D and the turnover rate of all metabolites and the parent vitamin in not only blood, but in several normal human tissues including intestinal mucosa, adipose tissue and liver. Metabolism studies will be carried out in certain pathological conditions where calcium metabolism is deranged and where it has been postulated that the abnormality may be due to an impaired action of the vitamin. These include: (a) humans with chronic renal failure, (including those with bilateral nephrectomy) before and after management with hemodialysis; (b) humans treated with glucocorticoids; and (c) humans with sarcoidosis; (d) humans with vitamin D-resistant rickets; (e) humans with hypoparathyroidism. In addition the biological effectiveness of 1,25-dihydroxycholecalciferol will be determined under nutritional balance conditions in states (a), (d) and (e) noted above.